Novel models to define the genetic basis of autism

Genetic studies have identified several loci, or stretches of chromosomal DNA, that are defective in individuals with autism. These loci contain more than one gene, so the next step is to identify the specific genes that are mutated. To that end, Alea Mills and her colleagues at Cold Spring Harbor Laboratory in New York propose to develop a series of mouse models carrying chromosomal defects analogous to those seen in individuals with autism.

The researchers generate these mice using a molecular biology technique called chromosome engineering, which takes advantage of the nearly identical order of genes in the mouse and human genomes. Previous studies had identified an autism-linked chromosomal defect in a region of the human genome known as 16p. After determining the boundaries of the affected area of human 16p, Mills and colleagues created the same genetic defect in mouse embryonic stem cells, which were then used to produce the mouse models.

With this technique, the researchers have been generating mouse strains that each have a different number of copies of the mouse genome region corresponding to human 16p. Through analysis of genetic, physiological and behavioral features, the investigators have observed symptoms in the mice analogous to those seen in people with autism. Based on these findings, Mills and her team are generating additional mice to hone in on the specific genes that are causing the phenotypes.

These mouse models will allow researchers to study the consequences of autism-linked genetic alterations using experimental approaches that would not be feasible in the clinic. The mice could also eventually be used to screen potential drug treatments for autism.